Five-year data from the Safety and Efficacy of Golimumab in Patients With Active Psoriatic Arthritis (GO-REVEAL) study suggest that golimumab maintains its safety and efficacy over the long-term, according to a new report.
Golimumab is an inhibitor of tumor necrosis factor alpha (TNF-alpha). Other drugs in this category include etanercept and infliximab. The new findings represent the "longest available clinical trial data of chronic anti-TNF treatment of [patients with psoriatic arthritis]," Arthur Kavanaugh, MD, professor of clinical medicine, University of California, San Diego, School of Medicine, and colleagues write in an article published online April 19 in the Annals of Rheumatic Diseases.
"These are the first longer-term data for psoriatic arthritis," Dr. Kavanaugh told Medscape Medical News. "As diseases such as [psoriatic arthritis] are chronic, it is important to have therapies that show sustained efficacy."
In the initial 24-week study, patients were randomly assigned to receive either subcutaneous injections of golimumab in doses of 50 or 100 mg every 4 weeks or placebo. After 24 weeks, all patients received 50 or 100 mg golimumab every 4 weeks for 5 years. Patients initially assigned to placebo were allowed to switch to the low dose of active therapy at 16 weeks and could escalate to the higher dose at week 52. Similarly, patients initially assigned to the 50-mg group could switch to the higher dose at week 16 or at week 52. Any patient receiving 100 mg could decrease to 50 mg after week 52.
To be eligible, patients had to have active psoriatic arthritis, defined as 3 more swollen or tender joints and plaque psoriasis with lesions of at least 2 cm in diameter, despite treatment with nonsteroidal anti-inflammatory drugs or disease-modifying antirheumatic drugs. They were naive to anti-TNF therapy. Patients were permitted, but not required, to use methotrexate during the study.
Of 405 patients initially enrolled, clinical and radiographic data were available for 267 patients by week 256 of the study. Outcomes at weeks 24, 52, and 104 have been reported previously.
Efficacy measures included 20%, 50%, or 70% improvement in American College of Rheumatology response (ACR20, 50, or 70); 50%, 75%, or 90% improvement in the Psoriasis Area and Severity Index; and psoriatic arthritis-modified Sharp/van der Heijde scores, which measure joint erosion in the hands and feet. The investigators also measured changes in disease activity, using the C-reactive-protein-based, 28-joint Disease Activity Score (DAS28-CRP).
At week 256, ACR20, ACR50, and ACR70 response rates were 62.8% to 69.9%, 43.4% to 50.7%, and 30.8% to 35.6%, respectively. The mean DAS28-CRP scores were 3.0 ± 1.4, 2.8 ± 1.2, and 2.8 ± 1.2 for patients in the placebo-then-active-drug group and the groups randomly assigned to receive 50 and 100 mg, respectively.
Among patients with enthesitis, mean baseline DAS28-CRP scores were 5.0 ± 4.1, 5.7 ± 4.0, and 6.1 ± 4.1 in the placebo, 50 mg, and 100 mg groups at baseline. By week 256, the scores had decreased to 2.4 ± 4.0, 1.9 ± 3.3, and 2.0 ± 3.4, respectively. Scores less than 2.6 suggest the disease is in remission, and scores higher than 5.1 signal high disease activity.
Similarly, among patients with dactylitis, mean scores at baseline were 3.1 ± 2.1, 6.3 ± 6.1, and 5.4 ± 6.7, respectively, declining to 1.2 ± 2.3, 1.3 ± 4.9, and 0.8 ± 2.1, respectively, by week 256.
In addition, the authors note that 52% to 58% of patients reported clinically meaningful improvements in physical function, as measured by the Health Assessment Questionnaire Disability Index. In addition, 60.8% to 72.2% of patients had a 75% or greater improvement in their Psoriasis Area and Severity Index from baseline to week 256, and between 39.2% and 56.5% had a 90% or greater improvement.
Changes in total psoriatic arthritis-modified Sharp/van der Heijde scores were seen in 63.0%, 62.4%, and 65.3% of patients, respectively, with mean changes of 0.3 or less, "suggesting a long-term effect of golimumab on inhibiting radiographic progression," the authors write.
There were no differences in the types of adverse events seen between doses. Of 394 patients included in the safety analysis, 347 (88.1%) experienced at least a single adverse event, including serious adverse events in 83 (21.1%) patients. Fifteen patients developed a total of 19 serious infections, and 13 major cardiovascular events occurred in 11 patients. Malignancies occurred in 21 patients, including 10 patients with nonmelanoma skin cancer.
Study limitations include the lack of a control group past 16 to 24 weeks and the dose changes that occurred in some patients, which limited the authors' ability to compare the 2 doses. They used an intention-to-treat analysis on the clinical data to control for these shortcomings, and radiographic analyses were performed only on patients with images available at baseline and weeks 104 and 256.
"Nice to See"
"For us as clinicians, it's really nice to see that these clinical responses hold up," said Elaine Husni, MD, who was not involved in the study. "Unlike most other studies, which end after 24 or 52 weeks, this one tells us about long-term safety and efficacy. It's also nice to know that 50 mg appears to work just as well as 100 mg on a long-term basis," she told Medscape Medical News.
Dr. Husni, vice-chair of rheumatology at the Cleveland Clinic in Ohio, also noted that the data on enthesitis and dactylitis were encouraging. "I think that's important because some of the earlier studies do not give a lot of information on those [with] enthesitis and dactylitis, and these can be a big problem in clinical practice. It's really nice to see that those scores improve with treatment," she said.
All in all, "this is a good study," said Dr. Husni, who also serves on the medical board of the National Psoriasis Foundation. "They looked at a good number of patients, they had a good number of parameters, and they followed them over a long length of time. I think it confirms our current regimen of anti-TNF drugs for [psoriatic arthritis], and it confirms the long-term safety and efficacy for these patients. So it certainly helps me feel comfortable about using these drugs in my patients over the long term."
The study was supported by Janssen Research & Development LLC and Merck/Schering-Plough Corporation. All authors have reported relevant financial relationships. Full conflict-of-interest information is available in the article. Dr. Husni has disclosed no relevant financial relationships.
Ann Rheum Dis. Published online April 19, 2014. Full text
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Cite this: Psoriatic Arthritis: Golimumab Safe, Effective at 5 Years - Medscape - Apr 29, 2014.